Care of the Patient with Open Angle Glaucoma

Transcription

1 The Care Process OPTOMETRIC CLINICAL PRACTICE GUIDELINE OPTOMETRY: THE PRIMARY EYE CARE PROFESSION Doctors of optometry are independent primary health care providers who examine, diagnose, treat, and manage diseases and disorders of the visual system, the eye, and associated structures as well as diagnose related systemic conditions. Care of the Patient with Open Angle Glaucoma Optometrists provide more than two-thirds of the primary eye care services in the United States. They are more widely distributed geographically than other eye care providers and are readily accessible for the delivery of eye and vision care services. There are approximately 36,000 full-time-equivalent doctors of optometry currently in practice in the United States. Optometrists practice in more than 6,500 communities across the United States, serving as the sole primary eye care providers in more than 3,500 communities. The mission of the profession of optometry is to fulfill the vision and eye care needs of the public through clinical care, research, and education, all of which enhance the quality of life.

2 OPTOMETRIC CLINICAL PRACTICE GUIDELINE CARE OF THE PATIENT WITH OPEN ANGLE GLAUCOMA Reference Guide for Clinicians Murray Fingeret, O.D., Principal Author Prepared by the American Optometric Association Original Consensus Panel on Care of the Patient with Open Angle Glaucoma: Gary L. Mancil, O.D., Principal Author Ian L. Bailey, O.D., M.S. Kenneth E. Brookman, O.D., Ph.D., M.P.H. J. Bart Campbell, O.D. Michael H. Cho, O.D. Alfred A. Rosenbloom, M.A., O.D., D.O.S. James E. Sheedy, O.D., Ph.D. Revised by: Murray Fingeret, O.D. December 2010 Reviewed by the AOA Clinical Guidelines Coordinating Committee: David A. Heath, O.D., Ed.M., Chair Diane T. Adamczyk, O.D. John F. Amos, O.D., M.S. Brian E. Mathie, O.D. Stephen C. Miller, O.D. Approved by the AOA Board of Trustees, March 20, Reviewed 2001, 2006, revised NOTE: Clinicians should not rely on the Clinical Guideline alone for patient care and management. Refer to the listed references and other sources for a more detailed analysis and discussion of research and patient care information. The information in the Guideline is current as of the date of publication. It will be reviewed periodically and revised as needed. American Optometric Association, N. Lindbergh Blvd., St. Louis, MO

3 TABLE OF CONTENTS INTRODUCTION... 1 I. STATEMENT OF THE PROBLEM... 3 A. Description and Classification of Open Angle Glaucoma Primary Open Angle Glaucoma Secondary Open Angle Glaucoma... 6 B. Epidemiology of Open Angle Glaucoma Incidence and Prevalence... 8 a. Primary Open Angle Glaucoma... 8 b. Secondary Open Angle Glaucoma Risk Factors a. General b. Ocular c. Nonocular d. Ocular Hypertension C. Clinical Background of Open Angle Glaucoma Natural History Common Signs, Symptoms, and Complications Early Detection and Prevention II. CARE PROCESS A. Diagnosis of Primary Open Angle Glaucoma Initial Glaucoma Evaluation a. Patient History b. Ocular Examination c. Supplemental Testing Follow-up Glaucoma Evaluation B. Diagnosis of Secondary Open Angle Glaucoma Pigmentary Glaucoma Pseudoexfoliation Glaucoma C. Management of Open Angle Glaucoma Basis for Treatment Available Treatment Options a. Medical (Pharmaceutical) Treatment b. Laser Trabeculoplasty c. Surgery d. Alternative Treatment Strategies e. Treatment of Pigmentary Glaucoma f. Treatment of Pseudoexfoliation Glaucoma Patient Education Prognosis and Follow-up a. Frequency of Follow-up b. Therapy Modification c. Effectiveness of Treatment d. Prognosis after Treatment of Secondary Open Angle Glaucoma Management of Patients with Severe, Irreversible Vision Loss CONCLUSION III. REFERENCES IV. APPENDIX Figure 1: Potential Components of an Initial Glaucoma Evaluation Figure 2: Optometric Management of the Patient with Primary Open Angle Glaucoma: A Brief Flowchart Figure 3: Frequency and Composition of Evaluation and Management Visits for Open Angle Glaucoma Figure 4: ICD-10-CM Classification of Open Angle Glaucoma Abbreviations of Commonly Used Terms Glossary

4 Introduction 1 2 Open Angle Glaucoma INTRODUCTION Optometrists, through their clinical education, training, experience, and broad geographic distribution, have the means to provide effective primary eye and vision care for a significant portion of the American public and are often the first health care practitioners to diagnose glaucoma. This Optometric Clinical Practice Guideline for the Care of the Patient with Open Angle Glaucoma is designed to provide optometrists with appropriate examination and treatment protocols to reduce the risk of visual disability from primary open angle glaucoma through timely diagnosis, treatment, patient education, and, when necessary, referral for consultation with or treatment by another health care provider. This Guideline will assist optometrists in achieving the following goals: Identify patients at risk of developing open angle glaucoma Accurately diagnose open angle glaucoma Improve the quality of care rendered to patients with open angle glaucoma Minimize the damaging effects of open angle glaucoma Preserve the gains obtained through treatment Inform and educate patients and other health care practitioners about the visual complications, risk factors, treatment options, and adverse reactions to treatments associated with open angle glaucoma.

5 I. STATEMENT OF THE PROBLEM Statement of the Problem 3 Glaucoma is not a single clinical entity but a group of ocular diseases with various causes that ultimately are associated with a progressive optic neuropathy leading to loss of vision function. About 8.4 million persons worldwide are bilaterally blind as a result of glaucoma (4, open angle glaucoma (OAG) and 3,936,241 angle closure glaucoma (ACG)), making it the second leading cause of bilateral blindness. The number of persons with open angle glaucoma in the United States, estimated at 2.2 million in 2004, is expected to rise as the population ages, to 3.36 million by An estimated 130,000 Americans are blind from glaucoma. 3 It is the third most common cause of blindness in the United States. 4-7 The Baltimore Eye Survey estimated the prevalence of glaucomatous blindness to be 1.7 per 1,000 in the general population, of which more than 75 percent was due to primary open angle glaucoma (POAG). 6 Over 11 percent of all blindness and 8 percent of all visual impairment may be due to glaucoma. 8 POAG is times more prevalent and accounts for about 19 percent of all blindness among African Americans, compared with 6 percent of blindness in Caucasians. 5,6 On average, it begins 10 years earlier in African Americans than in Caucasians. The Los Angeles Latino Eye Study (LALES) has shown that older Latinos' risk of developing open angle glaucoma (OAG) is comparable to that for African Americans, starting at the age of Information on the prevalence of blindness from glaucoma is inadequate because of the lack of a standardized definition of blindness across studies, and because not all blind people are included in blindness registries. 8,10 Therefore, these estimates may be 23 times less than the true prevalence. 5 Periodic comprehensive eye examination is the most cost-effective approach to detecting glaucoma in a high-risk population. A. Description and Classification of Open Angle Glaucoma Glaucoma can be classified as primary when it is not related to another underlying condition. Secondary glaucoma results from another ocular or systemic disease, trauma, or the use of certain drugs. The glaucomas can also be classified, on the basis of anatomy of the anterior chamber 4 Open Angle Glaucoma angle of the eye, as either OAG or angle closure glaucoma (ACG). 11 This Clinical Practice Guideline focuses on OAG (see Appendix Figure 4 for ICD-10-CM classification of OAG). 1. Primary Open Angle Glaucoma POAG is a chronic, progressive disease that most often presents with characteristic optic nerve (ON) damage, retinal nerve fiber layer (NFL) defects, and subsequent visual field (VF) loss. OAG occurs primarily in adults and is generally bilateral, but not always symmetrical, in its presentation. The majority of persons with POAG have elevated intraocular pressure (IOP). Although 21 mm Hg is considered the upper limit of statistically normal IOP, at least one-sixth of patients with POAG have IOP levels below 21 mm Hg, which is considered statistically normal in the 95 th percentile range. 4,12-14 Moreover, some whose IOP levels are statistically abnormal (>21 mm Hg) have no evidence of ON damage or loss of vision function, a condition known as ocular hypertension (OH). OAG in which the IOP is below a certain level, typically 21 mm Hg, is known as normal tension glaucoma (NTG). Historically, this has also been referred to as "low tension glaucoma" (LTG). The elevated IOP observed in the classic presentation of POAG usually results from decreased outflow of aqueous fluid from the eye. Though not well understood, this elevation in IOP is thought to be due to resistance within the trabecular meshwork. It may be attributable to acceleration and exaggeration of normal aging changes in the anterior chamber angle, iris, and ciliary body tissues of the eye These changes include loss of trabecular endothelial cells, increased pigment accumulation within these endothelial cells, thickening or fusion of the trabecular lamellae, thickening of the scleral spur, increased extracellular plaque material in the anterior chamber angle, and loss of ability of the endothelial cells lining Schlemm's canal to form giant vacuoles. 18 The etiology of glaucoma has been described as mechanical or vascular. The mechanical process involves compression of the axons due to elevated IOP. The vascular process includes events in which reduced blood flow to the posterior pole leads to damage. Whether mechanical or

6 Statement of the Problem 5 vascular, or both, compromise of the ganglion cell axons at the level of the lamina cribrosa leads to apoptosis or genetically programmed cell death Cellular damage activates proteins that control at least two key genes, one that inhibits apoptosis (bcl-2) and one that promotes cell death (bax). 21 These genes, in turn, affect a cascade of cellular events that result in the death of ganglion cells. At least two stimuli appear to activate the process of ganglion cell apoptosis in glaucoma: neurotrophin deprivation 22 and glutamate toxicity. 23 Blockage of retrograde axonal transport prevents the normal movement of neurotrophic factors from the brain to the ganglion cell body. 19 These peptides normally bind to the cell surface receptors of the ganglion cells and stimulate molecular events that affect essential functions of cell metabolism. Disruption of axonal transport compromises the ganglion cell and stimulates apoptosis at normal IOP; elevated IOP increases this response. Müller cells play a critical role in maintaining transport systems in the retina, 24 by keeping the normal excitatory protein glutamate at low levels. 25 In response to hypoxia or ischemia as a result of high IOP, ganglion cells primary response is excessive production of glutamate, which overrides Müller cell control. The resulting high levels of glutamate overstimulate N-methyl-D-aspartate receptors, leading to a cascade of molecular events that result in apoptosis: Calcium channels in the ganglion cell membrane open up, causing an overload of calcium, 25 which activates the enzyme nitric oxide synthase, leading to the formation of excessive levels of nitric oxide, and, finally, cell death Excitotoxicity, a process in which neurons are stimulated to death, involves mainly glutamate, although other excitatory amino acids may participate. 25,30,31 Investigators have discovered increased levels of nitric oxide in the optic nerve head (ONH) 32 and elevated levels of glutamate in the vitreous 26 of patients with POAG. Although lowering IOP may remove the primary mechanical or vascular insult to the ganglion cell axons of the retina, destruction of the surrounding tissue (secondary axonal degeneration) proceeds because of the creation of an excitotoxic environment, and the result is continuing apoptosis. This 6 Open Angle Glaucoma excitotoxicity may help explain why some glaucoma patients continue to show damage even after reduction of IOP to a level expected to control the disease process. 2. Secondary Open Angle Glaucoma The cause of secondary OAG can be any of a variety of substances that mechanically block the outflow of aqueous through the trabecular meshwork, resulting in elevated IOP. These substances include pigment, exfoliation material, and red blood cells. Secondary OAG can also result from alterations in the structure and function of the trabecular meshwork, due to insults such as trauma, inflammation, and ischemia. 11 Two conditions frequently contribute to the development of secondary OAG. Pigmentary dispersion syndrome (PDS). A condition in which pigment is released from the back surface of the iris and is deposited onto structures in the anterior and posterior chambers of the eye, PDS causes the development of pigmentary glaucoma (PG) in some persons. PDS occurs when the posterior iris rubs against the zonules of the lens or the ciliary processes, mechanically damaging the pigment epithelium of the iris and releasing pigment. 36 The concept of reverse pupillary block has been proposed to explain the anatomic abnormalities that lead to iris concavity, which can result in PDS. 37,38 Reverse pupillary block may occur momentarily during each lid blink. 39 A concave iris configuration similar to that in PDS can also be induced by accommodation. 40 A correlation between pigment release and elevated IOP with worsening glaucoma has been reported in patients who have PDS and PG. 41 It has been proposed that the trabecular endothelium phagocytizes the pigment and damages the cells, possibly via cellular toxicity, and causes them to drop off the trabecular lamellae. The denuded trabeculae no longer function properly and possibly collapse, obstructing aqueous outflow. 42

7 Statement of the Problem 7 Not everyone with excess pigment in the trabecular meshwork develops glaucoma. Dense pigmentation of the trabecular meshwork can exist for as long as 20 years without IOP elevation or abnormal outflow. 43 When pigment is released into the anterior chamber, other events ensue. Eyes that develop elevated IOP have difficulty managing the excess pigment load. PG may also be due to congenital abnormality of the anterior chamber, 44 and it can exist as a variant of POAG. 45 Pseudoexfoliation syndrome (PES). The presence of flaky or dandruff-like grayish-white exfoliative material in the anterior and posterior chambers of the eye, 46,47 and in the conjunctiva and orbit, is called pseudoexfoliation syndrome. This material accumulates on the ciliary epithelium, zonules, lens, posterior iris epithelium, intrastromal iris blood vessels, 50 anterior chamber angle, and corneal endothelium. 51 Exfoliative deposits are associated with degeneration of the ciliary epithelium, zonules (zonular dehiscence and lens subluxation), 52 and posterior iris epithelium (pigment dispersion, poor pupil dilation, posterior synechiae) The actual source of the fibrillogranular pseudoexfoliative material, which is similar to amyloid in composition, 54 appears to be various basement membranes of the eye, 55,56 including the lens capsule. 57 PES may represent abnormal basement membrane production at multiple sites by aging epithelial cells, 56 or it may be linked to microfibrils in the elastic elements of connective tissue. 58 Persons with PES have a higher prevalence of OAG than those without PES. 46,47 Elevated IOP in pseudoexfoliation glaucoma (PEG) probably occurs because of direct mechanical blockage of aqueous outflow from the anterior chamber by pseudoexfoliative material and pigment granules, or because of dysfunction of the trabecular endothelium 56 or high aqueous protein levels. 64 Some persons with PES maintain normal IOP, despite massive deposits in the trabecular meshwork, 65 possibly as a result of 8 Open Angle Glaucoma decreased aqueous production secondary to degeneration of the ciliary epithelium. 51 B. Epidemiology of Open Angle Glaucoma 1. Incidence and Prevalence a. Primary Open Angle Glaucoma An estimated 2.22 million Americans have OAG, 2 although at least half of all cases may be undiagnosed. 66 Seven times more prevalent than ACG in western populations, 67 POAG accounts for approximately 70 percent of all adult glaucoma cases. 8 One-fourth of all cases of OAG in America are African American. 68 Variously estimated as percent for Caucasians, 12,13,67,69-74 the prevalence of POAG in persons over age 40 was 1.7 percent for Caucasians and 5.6 percent for African Americans in the Baltimore Eye Survey. 67 The LALES showed the prevalence of OAG for Latinos to be 4.74 percent and that of ocular hypertension (OH), 3.56 percent. The prevalence of both OAG and OH was higher in older Latinos, with no gender relationships. Latinos' risk for OAG increases significantly with age. The prevalence of OAG in Latinos is similar to the prevalence in African American among groups of persons ages 60 and older. 9 The Framingham Eye Study calculated the prevalence of POAG in people ages 5285 years as 1.65 percent. 4 When VF testing was added to the screening of a subset of Framingham subjects, the prevalence of POAG rose to 2.1 percent. 75 While various studies show that the prevalence of cases with high IOP and VF defects is consistently between 0.3 and 0.4 percent, 8 the prevalence of NTG ranges from 0.05 to 0.79 percent. 4,13,76,77 The existing data are inadequate for determination of the precise incidence of glaucoma, 8,10 and estimates vary. Five-year incidence rates for Caucasians, calculated using pooled data, translate to 4060 cases per 100,000 persons per year at the age of 55 years and cases per 100,000 per year at age ,78 Pooling data on African Americans

8 Statement of the Problem 9 10 Open Angle Glaucoma results in estimates 4 times higher at age 55 (263 per 100,000 per year) and twice as high at age 75 (541 per 100,000). 68 A similarly high incidence among blacks was confirmed by direct observation in the Barbados Eye Study. 79 Because the prevalence of many glaucomas is strongly related to age, the growth of the elderly population will dramatically increase the incidence of the disease and the absolute number of persons with glaucoma who will need care in the future. The Baltimore Eye Survey found that 78 percent of people over the age of 40 have IOP above 21 mm Hg on a single tonometric reading. Using the 1990 census, the survey provided support for the estimate that 78 million Americans over the age of 40 have OH. 13,76,77 An estimated percent of persons with OH develop evidence of ON damage per year 80 ; however, the majority of those with OH will probably not develop glaucoma. 4,12,13,81 The Ocular Hypertension Treatment Study (OHTS) has shown that, while this estimate may be correct, new modeling based upon an assessment of risk factors enables prediction of which individuals are at greatest risk for converting to glaucoma. In fact, risk assessment shows that some individuals may have risks as great as 10 percent per year for converting to glaucoma b. Secondary Open Angle Glaucoma Pigmentary dispersion syndrome. PDS occurs in about 2.5 percent of adult Caucasians in the United States. 86 It occurs less commonly in African Americans and Asians. About 2060 percent of persons with PDS develop OH; 2550 percent, PG. 86,87 Pigmentary glaucoma constitutes about 4.4 percent of all glaucomas 86,88 and 12.5 percent of OAGs. 86 PDS is usually bilateral and affects persons at younger ages than POAG (3050 years) Its occurrence is most common in Caucasian males with myopia In fact, about 90 percent of individuals with PDS are myopic. 91 PDS may have an autosomal-dominant, multifactorial basis, suggesting the importance of family history. 88,92,93 At least one genetic locus has been identified for PDS. 94 Pseudoexfoliation syndrome. The prevalence of pseudoexfoliation syndrome varies widely throughout the world, 95 with estimates ranging from about 1.6 to 2.3 percent in persons over age 50 in the United States. 96,97 The prevalence of PES with subsequent PEG increases with age, and these conditions most commonly occur between the ages of 60 and ,97 PES is 23 times more common in women than in men, and its prevalence is much lower in African Americans than in Caucasians. 96,100 Family studies are investigating several putative sites on chromosome 2 for genetics related to PES. 101 PES has been reported to be unilateral at initial diagnosis in 5070 percent of cases, 97-99,102 a prevalence that may be overstated due to inadequate evaluation. 102 Unilateral PES may actually occur at a younger age as a precursor to the involvement of both eyes. 59,969 In 1315 percent of cases of unilateral PES, involvement of the other eye is discovered during 1015 years of follow-up. 60,103 Thus, it appears that unilateral PES is rare, but more often asymmetric at a subclinical level. 103 PES is a definite risk factor for OH and OAG. 59,98,99 Initial screening has found OH in 2230 percent of individuals with PES. 59,104 OH develops in about 10 percent of persons who had PES and normal IOP at initial diagnosis. The cumulative probability of developing OH is 5.3 percent in 5 years and 15.4 percent in 10 years. 99 The prevalence of PES in a glaucoma population ranges from 1.6 to 28 percent in the United States. 60,96,100,105,106 Among persons with PES, percent reportedly develop OAG. 96,104 The Early Manifest Glaucoma Trial (EMGT) showed that after a mean follow-up of 8.7 years, 55.1 percent of individuals with PES and OH developed OAG, compared with 27.6 percent who had OH only. The glaucoma conversion ratio was twice as high when other factors were matched for individuals with PES and OH. 107

9 2. Risk Factors a. General Statement of the Problem 11 Age. Age is a major risk factor for the development of glaucoma. The prevalence of glaucoma is 410 times higher in the older age groups than in persons in their forties. 4,13,67 In the Collaborative Glaucoma Study, the incidence of VF loss from glaucoma rose with age, from 0.7 percent in persons under the age of 40 years to 4.8 percent in persons age 60 and over. Damage to the ON from glaucoma is uncommon before the age of 50 in Caucasians, but it appears to occur at least a decade earlier in African Americans. 108 Race. Race is another major risk factor for POAG. African Americans develop the disease earlier, do not respond as well to treatment, are more likely to require surgery, and have a higher prevalence of blindness from glaucoma than Caucasians. 67, The age-adjusted prevalence of POAG was 4.3 times greater in African Americans than in Caucasians in the Baltimore Eye Survey. 67 Studies in St. Lucia 113 and Barbados 114 found POAG in 716 percent of blacks over age 40. Although the prevalence of NTG has been reported to be high in Asians, 115 this rate may be influenced by the accuracy of tonometry in this ethnic group. 116 Older Latinos' risks of developing OAG are comparable to those of African Americans, starting at the age of 60 years. 9 Family History. The etiology of glaucoma most likely involves multifactorial or polygenic inheritance mechanisms Studies have suggested that 1325 percent of patients with glaucoma have positive family histories for the disease In close relatives of persons with POAG, the prevalence is 36 times that of the general public, 117 and the incidence of the disease in first-degree relatives is 35 times the rate in the general population. 119,120 The 22 percent lifetime risk for glaucoma in relatives of patients with glaucoma is almost 10 times that of controls. 127 The risk may be greater in siblings than in parents or children. 126,127 A family history of glaucoma places a person with OH at greater risk of developing the disease. 128,129 Ocular characteristics associated 12 Open Angle Glaucoma with glaucoma, including IOP 122,130 and the cup-to-disc (C/D) ratio, 131 have been associated with moderate familial risk. Mutations in transcription factor genes are responsible for developmental disorders associated with glaucoma. 132 Although POAG is not an obvious developmental problem, the finding that adult-onset glaucoma results from mutations in the same genes that cause developmental defects such as juvenile glaucoma supports such a relationship. 133 Many forms of POAG probably result from a combination of mutations in more than one gene. 133,134 Among at least six major genes for glaucoma that have been localized, 133 certain mutations have a higher incidence in specific types of OAG. 135 POAG is not likely inherited as a single gene but rather as a complex trait. More than 30 mutations of the myocilin (MYOC/TIGR) gene have been associated with POAG in different ethnic populations throughout the world. 136 A myocilin gene mutation may be present in 35 percent of patients with OAG. 137,138 The presence of myocilin in the ON axons and lamina cribrosa astrocytes suggests that the trabecular meshwork might not be the only target for abnormal myocilin GLC1A-linked OAG. 136 Eventually, glaucoma treatment may involve inhibiting the expression of this gene. At present, genetic counseling usually includes providing information about the risks for persons whose close relatives have glaucoma. 117 There is no conclusive evidence that gender is a risk factor for glaucoma. 10,139 b. Ocular Intraocular pressure (IOP). IOP has a strong, direct relationship with the prevalence and long-term risk for glaucoma. 8,10,125,140 For persons with IOP above 21 mm Hg, the risk of developing glaucoma is 16 times the risk for persons with IOP below 16 mm Hg. 4,14 Moreover, the percentage of eyes developing VF defects after 5 years is 6.7 percent for those with IOP over 20 mm Hg,

10 Statement of the Problem 13 compared with 1.5 percent of eyes with IOP below 20 mm Hg. 108 Even in NTG, the higher the pressure, the greater the risk. 141,142 Asymmetric levels of IOP in individual pairs of eyes correlate with asymmetric damage to the ON. 141,142 Lowering the IOP reduces the risk for ON damage. 143 Long-term studies have consistently shown that a large percentage of persons with statistically elevated IOP (>21 mm Hg) do not develop glaucoma, 4,12,13,76,77, 80,108,144,145 while many persons with glaucoma have IOP well within the statistically normal range. 4,13,14,81 Population-based studies have demonstrated that one-tenth or fewer of those with elevated IOP suffer VF loss when monitored over several years. 4,12,13,76 The incidence of glaucoma among persons with OH is at most 1 percent per year. 80,144,145 One-third to one-half of persons with glaucoma have IOP at or below 20 mm Hg at initial diagnosis. 4,12,13,76,108 The Barbados Eye Study showed a relationship between baseline IOP and the development of glaucoma. Among persons who developed glaucoma, 46 percent had baseline IOPs exceeding 21 mm Hg. The risk for OAG increased by 12 percent for each 1 mm Hg increase in IOP. The incidence of OAG increased from 1.8 percent for persons with baseline IOP less than 17 mm Hg to 22.3 percent for those with baseline IOP exceeding 25 mm Hg. 146 Several studies have addressed the question of which IOP measurement is most important mean IOP, highest IOP measurement, or IOP fluctuation. Mean IOP has consistently been associated with the development of glaucoma, while the data related to fluctuation of IOP in relation to true IOP are conflicting Corneal thickness. The OHTS showed a relationship between corneal thickness and the development of OAG. Thin corneas were at a greater risk of developing glaucoma (hazard ratio [HR], 1.71 for each 40 μm change in cornea thickness). 83 African Americans had thinner corneas, and a thin cornea influenced the accuracy of tonometry measurement. 150 The OHTS also showed 14 Open Angle Glaucoma that, although for individuals with OH the risk of developing OAG is approximately 1 percent per year, those with increased central corneal thickness (CCT) may have a much higher risk. 83 Evaluation of each individual for key risk factors age, IOP, vertical C/D ratio, VF status, and CCT will provide a better idea of who is at a higher risk for OAG. Visual field loss. In the Malmo Ocular Hypertension Study to evaluate the importance of baseline risk factors for development of glaucomatous VF loss in patients with high-risk OH, the investigators randomized 90 patients to topical timolol or placebo treatment and observed them prospectively for up to 10 years. Eligibility criteria were elevated IOP, open angles, and normal VFs plus at least one extra risk factor (suspect disc or known disc hemorrhage; positive family history of glaucoma, PES, or PDS; diabetes; or mean IOP 27 mm Hg). The researchers evaluated the risk factors as well as the mean baseline IOP and IOP fluctuation, sex, age, and blood pressure as predictors for development of reproducible glaucomatous VF loss. In addition to the prospective data, they retrieved post-study data from patients' records, extending maximum follow-up to 17 years. Thirty-seven patients developed glaucomatous VF loss. Of all factors included in the analysis, those emerging as significant risks were disc appearance, older age, and higher IOP. Suspect disc appearance increased the risk approximately threefold (HR, 2.90; 95% CI, ). The hazard ratio was 1.05 (95% CI, ) per year of age, while mean baseline IOP increased the risk in patients by 14 percent per mm Hg (95% CI, ). Patients with OH were at higher risk of developing glaucomatous VF loss in the presence of suspect discs, high IOP, and older age. 151 Various optic nerve (ON) characteristics can be considered clinically as both risk factors and criteria for the detection and assessment of the progression of glaucoma. These features relate to the size and shape of the optic cup, the thickness and uniformity of the neuroretinal rim, 140, and the symmetry of the optic cups. 155

11 Statement of the Problem 15 Though potentially subject to selection bias, several studies have demonstrated, after adjustment for age, a twofold to fivefold higher prevalence of POAG in patients with myopia. 128,156,157 c. Nonocular Diabetes mellitus. The association of diabetes mellitus with the development of both elevated IOP and POAG has been controversial. 139 Several studies lend support to a higher prevalence of OH 158 and POAG in persons with diabetes, for whom the relative risk for POAG ranges from 1.6 to ,166,167 Others have found no relationship, or that the presence of diabetes even has a protective effect against the development of OH or 83,108,125,129,140,158,166, POAG. Vasospasm. Vasospasm is one possible mechanism for, or as a factor contributing to, ON damage in glaucoma. 171,172 This theory is supported by evidence of an association of NTG with migraine headaches and Raynaud's syndrome. 173 The literature is equivocal on an association between systemic hypertension and POAG. 10,125,140,158,166,167,169,174 The Baltimore Eye Survey suggested the complexity of the relationship between POAG and systemic blood pressure. 175 Patient age and the duration of the hypertension modified the effect of systemic blood pressure on POAG. Lower perfusion pressure (BP-IOP) was significantly associated with an increased prevalence of POAG. Low systemic blood pressure, 176,177 including the nocturnal dip, 176,178,179 also may pose a risk for NTG and OAG. The EMGT and the Barbados Eye Study revealed a relationship between lower systolic perfusion pressure and the development or progression of OAG. 180, Open Angle Glaucoma patients whose C/D ratios were under 0.4 (350 ± 184 au) than in the 10 OH patients who had higher C/D ratios (203 ± 79 au; P = 0.039). Conversely, peripapillary retinal blood flow did not correlate significantly with any clinical parameter. Blood flow in the ONH was significantly lower in the OAG patients than in the OH patients and normal volunteers. The authors found no significant differences in ONH blood flow between patients with OH and normal volunteers, and peripapillary retinal blood flow did not differ significantly across groups. The inverse correlation of neuroretinal rim blood flow and increased C/D ratio was significant. Patients with OH who had higher C/D ratios demonstrated significantly lower rim blood flow than those whose C/D ratios were lower, suggesting the importance of reducing rim perfusion in persons with high-risk OH before the manifestation of VF defects. 182 d. Ocular Hypertension When the criterion for OH is 20 mm Hg or higher, the prevalence of OH increases with age, from less than 5 percent of persons under age 40 to 20 percent or more of persons over age 70. 4,14,76,77 Age-controlled data analysis has shown a higher prevalence of OH in African Americans than in Caucasians. 109 The general, ocular, and nonocular risk factors for POAG are summarized in Table 1. C. Clinical Background of Open Angle Glaucoma 1. Natural History Perfusion pressure ratio. A study using full-field perfusion analysis of scanning laser Doppler flowmetry images to compare ONH and peripapillary retinal blood flow in eyes with OAG and OH with normal eyes showed an association between reduced blood flow and OAG. Neuroretinal rim flow values showed a significant inverse correlation with C/D ratio (P = 0.001). Mean neuroretinal rim blood flow was significantly higher in the 10 OH ON damage in glaucoma has traditionally been attributed to the tissue's inability to continue to tolerate a certain IOP. Initially, the axons of the ganglion cells of the retina are destroyed at the level of the lamina cribrosa scleralis There are two theories concerning how this specific damage occurs. One stresses the reduction in blood flow to the axons 186 ; the other is based more on mechanical damage as the axons pass through the lamina cribrosa scleralis. 184,187 The premise for both

12 Statement of the Problem 17 Table 1 Risk Factors for Primary Open Angle Glaucoma General Ocular Nonocular Age Race Family history Elevated or asymmetric levels of IOP Diffuse or focal enlargement of cup portion of optic nerve Diffuse or focal narrowing of neuroretinal rim Asymmetry of cup-to-disc ratios >0.2 Myopia Central corneal thickness Visual field status (pattern standard deviation) Diabetes mellitus Vasospasm Perfusion pressure ratio hypotheses involves abnormality either abnormal IOP or the axons abnormal susceptibility to damage when the IOP is normal. Untreated or inadequately treated glaucoma will progress to the point that loss of visual function results in disability or blindness. 188,189 Once glaucomatous damage has occurred in one eye, the risk for damage in the other eye increases. 190 The rate of progression varies significantly, depending on the IOP, the ON s susceptibility to damage, and the severity of the disease. Untreated glaucoma may cause blindness in 315 years, depending on the IOP. 189 There is great variability in the susceptibility of the ON to glaucomatous damage. Some persons with relatively low IOP (NTG) incur ON damage, while others with rather high IOP (OH) never show such damage. Even with the most sensitive clinical test available, the earliest unequivocal indication of loss of function may not be detectable until at least one-fifth of the ganglion cell axons of the retina have been destroyed and there is a uniform 5-decibel (db) decrease in threshold across the entire VF. 191 The authors of a study showing a 25 percent loss 18 Open Angle Glaucoma of retinal ganglion cells in patients for whom threshold automated perimetry revealed a 5-dB loss of retinal sensitivity concluded that at least a 2535 percent loss of ganglion cells is associated with typical clinical criteria for detecting abnormalities Common Signs, Symptoms, and Complications Patients in the mild or moderate stages of OAG seldom have symptoms or complaints. When the disease progresses to the severe stage, some patients may present with symptoms or complaints related to restricted VF or reduced vision. Glaucoma patients' more common symptoms, complications, and complaints are associated with the side effects, inconvenience, and cost of medications to treat the disease. 3. Early Detection and Prevention There is no scientific evidence of any method of preventing OAG, nor is there any absolute way to predict who will develop the disease later in life. 8 The presence of certain ocular, systemic, and general risk factors increases the probability that a person will develop glaucoma. Among these risk factors, only IOP can be altered. 8 Large population screenings seem ideal for detecting diseases, such as OAG, that have a high prevalence, cause vision disability, and are asymptomatic. Moreover, patients can benefit from early treatment. 143,193,194 Unfortunately, techniques to screen for glaucoma lack the sensitivity or specificity to be effective, due to significant overlap in affected and unaffected individuals results on key clinical tests. 139, Even screening protocols using multivariate predictive models do not adequately distinguish between persons affected and unaffected by glaucoma. 194 Glaucoma screening procedures may include, but are not limited to: Tonometry. Measurement of IOP is not a reliable screening procedure for detecting glaucoma. 194,197,198 No level of IOP provides the necessary balance between sensitivity and specificity. 194 Moreover, as many as one-half of persons with glaucoma may have IOPs below 22 mm Hg at screening, 4,13,67,108

13 Statement of the Problem 19 and most with elevated IOPs do not have, and may never develop, glaucoma. 4,80,144,145 The EMGT showed that increased IOP fluctuation was not an independent factor for the progression of glaucoma. The median follow-up time was 8 years (range, years) with 68 percent of the patients progressing. Follow-up of IOP and IOP fluctuation in the same time-dependent model showed that mean IOP was a significant risk factor for progression (HR, 1.11; 95% CI, ; P < ). IOP fluctuation was not related to progression (HR, 1.00; 95% CI, ; P = 0.999). EMGT results confirm that elevated IOP is a strong factor for glaucoma progression: The HR increased by 11 percent for every 1 mm Hg of increase in IOP. IOP fluctuation was not an independent risk factor for the progression of glaucoma, a finding that conflicts with earlier reports. One explanation for the discrepancy is that the EMGT analyses did not include postprogression IOP values, which would be biased toward larger fluctuations because of more intensive treatment. 148 Optic nerve assessment. Despite pronounced ON cupping in eyes that eventually develop glaucoma, the clinical finding of a 0.6 C/D ratio has only about a 60 percent (41%77%) sensitivity for predicting which cases of OH will convert to the disease There is no cutoff value for the C/D ratio that would change this conclusion. 194 Determining the C/D ratio by direct ophthalmoscopy is even less precise, due to intraobserver and interobserver variability. 4,199,202 The evidence suggests even greater variability in assessment of the notching or width of the neuroretinal rim. 199 The topography of the ON and configuration of the neuroretinal rim may be more sensitive and specific than the C/D ratio in the detection of glaucoma. 203 The preferred method of assessing the ON and evaluating the cup and neuroretinal rim tissue is to use a fundus lens and biomicroscope to obtain a dilated-pupil stereoscopic view of the ON. Using optical coherence tomography (OCT) parameters to facilitate identification of glaucomatous damage and evaluation of 20 Open Angle Glaucoma differences between normal eyes, eyes with OH, and those with glaucoma, research showed that mean retinal NFL thickness around the disc and superior and inferior retinal NFL thicknesses were significantly less in glaucomatous eyes than in eyes with OH or in normal eyes (P < 0.001). Rim parameter values were significantly lower in glaucomatous eyes than in normal (P < 0.001) and OH eyes (P = 0.01). C/D ratios were significantly higher in glaucomatous eyes than in OHT (P < 0.001) and normal (P < 0.001) eyes. The differences between normal and OH eyes were significant for seven disc parameters. There were no differences across groups for parameters describing retinal NFL asymmetry between the eyes. The average ratio of change (AROC) curves representing the average rate of change of the other NFL and disk parameters ranged from to Results obtained using the Stratus OCT differed significantly for almost all NFL and disc parameters, thus clearly discriminating between glaucomatous and normal eyes. Although the authors found significant differences between ON parameters in normal and OH eyes, there were no differences between their retinal NFL parameters. 204 Evaluation of OCT findings for the detection of early glaucoma showed that one eye from each of 50 normal persons, 42 glaucoma suspects (GS), and 59 patients with early glaucoma diagnosed on the basis of VF defect (EGVF) met the following VF criteria: VF mean deviation at least 6.00 db, age 40 years, spherical refractive error 5 diopters (D), astigmatism 3 D, and visual acuity 20/30. Average nerve fiber layer thicknesses (NFLT) were ± 15.4, ± 25.4, and 86.5 ± 31.5 µm in normal, GS, and EGVF eyes, respectively. Normal eyes were different from eyes in both glaucoma groups (P < 0.001); NFLT in the superior quadrant and at the 11 o'clock position had the highest area under the receiver operating characteristic curve (0.840 and 0.933) in the GS and EGVF groups (P = 0.03). The sensitivity of OCT for detection of glaucoma was 71 percent for the GS group and 85 percent for the EGVF group, with specificity fixed at 90 percent. Although the OCT discriminates well between normal

14 Statement of the Problem 21 eyes and those with early perimetric glaucoma, its performance is less adequate in eyes with suspicious discs and normal VFs. 205 Photography. Stereoscopic fundus photography is useful for evaluating the ON, because it reduces observer variability in assessment of the C/D ratio 199. However, stereoscopic fundus photography assessment of the horizontal or vertical C/D ratio, or of the narrowest neuroretinal rim width, does not achieve a sensitivity-specificity balance adequate for screening. 194 Photography may be of value in assessing the NFL, 203 except that media changes common in the age groups screened for glaucoma diminish the quality of the photographs. 193 The sensitivity and specificity of NFL assessment are highest when the photographs are of high quality. 207,208 Perimetry. The use of automated perimeters for mass screenings has not been practical because of the size and cost of most modern instruments. 193 In the past, perimetry results from mass screenings were quite variable. 209 For example, use of the Henson perimeter test yielded a very high number of false-positive findings for glaucoma in the Beaver Dam Eye Study. 70 Frequency doubling technology (FDT) perimetry has proven effective in screening for glaucoma. The Glaucoma Advisory Committee of Prevent Blindness America has determined that a VF test to screen for glaucoma should have 95 percent specificity, compared with standard automated perimetry, and 85 percent sensitivity for moderate to advanced VF loss. 210,211 The sensitivity and specificity of FDT vary, depending on the mode of testing (screening vs. thresholding) 210,211 and the severity of the disease in the population being tested. For moderate and advanced glaucoma, FDT has sensitivity 212 and specificity values 210,211, above 90 percent for detecting glaucomatous VF loss. FDT sensitivity in the detection of early glaucomatous damage has been lower and more variable between studies. 210,211,213, Open Angle Glaucoma FDT perimetry has demonstrated better patient reliability, 217 less intratest and intertest variability, 218 and results that are comparable to or better than standard automated perimetry for the detection of glaucoma. 213,217 It appears that FDT can facilitate diagnosis and grading of the extent of glaucoma. 219 Despite the availability of new technologies for NFL assessment, threedimensional imaging of the ON, and VF testing, periodic comprehensive eye examination may be the most cost-effective way to detect glaucoma in a high-risk population. A relevant question is whether glaucomatous damage occurs first to the structure of the eye (ON/NFL) or to its function (as assessed by perimetry). A study seeking age-related structural and functional changes used pattern electroretinogram (PERG), perimetry, and retinal tomography to examine 34 normal subjects and 40 patients with glaucoma and found little difference, depending upon the scale of the test used. The unit of differential light sensitivity (DLS) in perimetry is the decibel. The investigators recorded transient and steady-state PERGs and measured peak-to-trough amplitude. Then they correlated the PERG amplitudes with decibel and 1/Lambert DLS for the central 18 degrees of the VF and with neuroretinal rim area in the temporal part of the optic disc. Examination of the correlation between variables by linear and quadratic regression analysis revealed a curvilinear relationship between decibel DLS and both PERG amplitude and neuroretinal rim area, as well as a linear relationship between 1/Lambert DLS and PERG amplitude and neuroretinal rim area. These findings support the hypothesis that there is no ganglion cell functional reserve but rather a continuous structure-function relationship, and that the impression of a functional reserve results from the logarithmic (decibel) scaling of the VF. 220

15 The Care Process Open Angle Glaucoma II. CARE PROCESS b. Ocular Examination This Guideline describes the optometric care provided to a patient with POAG. The components of patient care described are not intended to be all-inclusive. Professional judgment and individual patient symptoms and findings may have significant impact on the nature, extent, and course of services provided. Some components of care may be delegated. Evaluation of a patient suspected of having OAG may include, but is not limited to, the following: Visual acuity (VA). Best corrected distance or near visual acuity, or both, should be measured as one indicator of the integrity of the central vision system. A. Diagnosis of Primary Open Angle Glaucoma Although POAG is not a curable disease, early diagnosis and adequate treatment are effective in reducing or preventing further ON damage. 143,153,221 The difficulty of distinguishing between eyes without glaucoma and eyes with early or subtle glaucoma is widely acknowledged. 222 Furthermore, there is no unanimous opinion on what constitutes the first signs of damage in glaucoma Initial Glaucoma Evaluation The initial glaucoma evaluation may include the tests and procedures of a comprehensive adult eye and vision examination,* in addition to some procedures specific to the differential diagnosis of glaucoma (see Appendix Figure 1). 224 Proper management of glaucoma requires longitudinal evaluation of established baseline data for important clinical parameters. 225 a. Patient History The patient history should include a thorough analysis of all general, familial, ocular, and nonocular risk factors for the various types of glaucoma. A complete medical history, including current medication and known medicine intolerance and allergies, is essential. *Refer to the Optometric Clinical Practice Guideline on Comprehensive Adult Eye and Vision Examination. Pupils. Careful evaluation of the pupils should be performed to reveal the presence of a relative afferent defect. 226 Biomicroscopy. Assessment of the cornea and structures of the anterior and posterior chambers, both before and after pupillary dilation, should be conducted to evaluate anomalies or abnormalities that could cause or contribute to a secondary increase in IOP. The anterior chamber depth should be estimated. Tonometry. Measurement of the IOP should precede pupillary dilation and gonioscopy. The instrument used, as well as the time of day at examination, should be recorded. Multiple measurements in each eye (serial tonometry) at various times of the day may help to evaluate diurnal variability. 227 Attention should be directed toward differences between the IOPs of the two eyes 142 and changes in pressure over time. 228 IOP tends to rise when a person lies down at bedtime (assumes a supine position), and it continues to rise during the nocturnal hours, irrespective of the decline in aqueous production during this period. IOP tends to peak around 5:30 a.m., just before awakening. Approximately 6 percent of IOP spikes occur outside traditional office hours. 229 Pachymetry. Measurement of the CCT with a pachymeter is indicated as part of the evaluation of the patient with glaucoma or the glaucoma suspect. The examiner should perform pachymetry on each eye, taking three or more measurements and using the mean of these measurements for each eye. IOP measurement by Goldmann applanation tonometry (GAT) assumes an average CCT of 520 µm. 230 Meta-analysis of values reported in the literature

16 The Care Process 25 indicates that normal individuals have a significant variation in CCT (0.535 ± µm), 231 which could influence the accuracy of this measurement. Research has indicated that the average corneal thickness is closer to 545 µm. In fact, cannulation studies have indicated that a 10 percent change in CCT can result in a mean change in IOP (measured by GAT) of 13.5 mm Hg. 232,233 A thick cornea may influence IOP measurement with non-contact tonometry more than with GAT. 234 One study evaluated whether patients with glaucoma with asymmetric CCT demonstrated greater VF loss in their thinner CCT eye than in their thicker CCT eye. 235 Of the 52 subjects who met all criteria for study inclusion, the mean Advanced Glaucoma Intervention Study (AGIS) 236 score was significantly higher in thinner CCT eyes than in thicker CCT eyes. Subjects with higher AGIS scores for their thinner CCT eyes outnumbered subjects with higher AGIS scores in their thicker CCT eyes, with the differences approaching statistical significance for the full sample (P = 0.06) and achieving significance when the analysis was limited to subjects with CCT asymmetry of at least 15 µm (P = 0.001). Multivariate logistic regression analysis identified thinner CCT as the primary risk factor associated with higher AGIS scores in subjects with CCT asymmetry 15 µm. These results correspond to prior reports implicating CCT as an independent risk factor for glaucomatous VF loss. When significant CCT asymmetry is present in patients with glaucoma, the thinner CCT eye is at greater risk for more advanced VF loss. 235 The objective of another study, conducted in subjects whose mean corneal thickness was 540 µm, was to determine the correlation of CCT to Goldmann applanation tonometry and dynamic contour tonometry (DCT, PASCAL) findings, and to glaucoma stage as assessed by C/D ratio. The corneal thickness values were lowest for African Americans and NTG patients (518 µm and 522 µm, respectively); their central corneas were significantly thinner than those of Caucasians (549 µm) and subjects with OH (564 µm). IOP assessed by GAT was significantly correlated with CCT (sample correlation coefficient [r] = 0.068, P < 0.001), whereas 26 Open Angle Glaucoma PASCAL was not significantly associated with CCT (r < 0.001, P = 0.997). There was a significant correlation (r = 0.13, P < 0.001) between increased IOP and the large ocular pulse amplitudes predominantly found in ocular hypertensive patients. The investigators also detected a significant negative correlation between C/D ratio and CCT (r = 0.102, P < 0.001). Thin central corneas are more likely to exist in patients whose glaucoma is at an advanced stage and among persons with NTG as well as persons of black African ancestry. Underestimation of IOP by GAT could be a causative factor for this finding. 237 To evaluate the association between NTG and CCT, researchers studied 56 eyes in 56 subjects with NTG and 84 eyes in a group of 84 subjects with no VF loss. They found a significantly thicker mean CCT for the group with no VF loss, compared with those for all three groups with glaucomatous VF loss (NTG). Multivariate regression analysis revealed a robust, independent, association between CCT and the presence of NTG-related VF loss. Conversely, there was no relationship between CCT and the severity of NTG-related VF loss. In eyes characterized by statistically normal IOP (measured by GAT), there was a significant relationship between CCT and the presence, but not the severity, of glaucomatous VF loss. 238 Many studies have demonstrated above-average CCT in some individuals classified as having OH and below-average CCT in some patients diagnosed with NTG. 240,241, ,249 On the basis of CCT, two studies reclassified 35 percent and 56 percent of cases of OH and 44 percent and 36 percent of those with NTG, respectively. 241,245 One study has recommended CCT measurement as a way to avoid overdiagnosis of OH patients with thick corneas and underdiagnosis of those with thin corneas. African Americans may have thinner central corneas than Caucasians, potentially resulting in underestimation of their actual IOPs. 250 Similarly, a decrease in CCT following in situ keratomileusis could result in underestimation of actual IOP. 251,252

17 The Care Process 27 Gonioscopy. Careful evaluation of the anterior chamber angle is essential for differentiating between open angle and closed angle glaucomas, and for distinguishing primary glaucoma from secondary glaucomas. Optic nerve assessment. Examination of the ON requires procedures that provide stereoscopic visualization with adequate magnification, through a dilated pupil if clinically appropriate. Use of a biomicroscope with an ancillary lens is the preferred procedure. A lens of 60, 66, or 78 D, or a fundus contact lens, enables the best stereopsis. Evaluation of the ON includes ruling out other potential causes of ON atrophy and other tissue abnormalities that might result in VF loss similar to that caused by glaucoma, especially in glaucoma suspects with IOP below 21 mm Hg. A stepwise process is often used to assess the optic disc and retinal nerve fiber layer in evaluating whether glaucomatous damage is present. This stepwise process includes assessing the optic disc for size, the health of the neuroretinal rim using the ISNT rule, and whether disc hemorrhages, peripapillary atrophy, or NFL defects are present. The ISNT rule states that in a healthy optic disc, the location of the thickest rim tissue is inferior, followed by superior, then nasal; the thinnest rim tissue is in the temporal quadrant. The significance of assessing for optic disc size is that a large disc will have a large C/D ratio, which may be natural for this disc size. A small disc rarely has a large cup; when present, it may be a sign of damage. The converse is also true in that, in the presence of a small disc, a low C/D ratio may be associated with glaucomatous damage. 253 The mean disk area varies depending upon race with larger disk size associated with individuals of African descent. 254 The average disc size is approximately mm 2, depending upon the study. 255,256 A study to evaluate whether the ISNT rule can differentiate normal from glaucomatous eyes enrolled 66 subjects (33 black, 33 white) with normal eyes and 43 subjects (15 black, 28 white) with OAG. The ISNT rule was intact for 52 (79%) of the normal eyes and Open Angle Glaucoma (28%) glaucomatous eyes (P < 0.001). Multiple logistic regression analysis yielded an odds ratio of 6.04 (95% CI, ) for glaucoma associated with violation of the ISNT rule, after adjustment for age. Race was not a confounder of this association. The ISNT rule is useful in differentiating normal from glaucomatous optic nerves and is unaffected by race. 253 Imaging of the ON and the retinal NFL has received increasing attention in the diagnosis and treatment of glaucoma. Among ON and retinal NFL imaging devices, which provide quantitative information, no single instrument outperforms any other in distinguishing subjects with glaucoma from healthy control subjects. Still, imaging does provide useful clinical information for evaluation with data from other components of the glaucoma examination. 258 Users of confocal scanning laser tomography (CSLT) have concentrated on the early identification of patients with glaucoma. The most beneficial application of this technology may be in the detection and monitoring of subtle changes in ON tissue over time. 259 Because of significant physiological variation of the ONH within the normal population, it is difficult, even with an ideal imaging system, to identify early glaucoma accurately in a single session. 259 The advantages of CSLT include the ability to obtain images without pupil dilation, 260 the use of low-intensity light, and realtime imaging. The major disadvantage is the dependence of measurements on the operator s subjective definition of a reference plane. Inflection-point analysis may help to alleviate this problem. 261 Despite the tendency with CSLT to overestimate the neuroretinal rim and to underestimate the C/D ratio, 262 studies have shown that the parameters generated by this technology are adequate for discrimination between normal ONHs and those of patients with OH 257 and early glaucoma. 263,264 CSLT has a sensitivity of 89

18 The Care Process 29 percent and a specificity of 84 percent for differentiating between normal eyes and those with early glaucomatous VF defects. 265 Longitudinal studies using CSLT have found that for various parameters measured over time, there are significant differences between OH and glaucoma patients with progressive VF loss and those with stable fields. 266,267 Optical coherence tomography (OCT) also allows the assessment of the ON in glaucoma. The advantages of OCT are similar to those of CSLT, although the reference plane is generated by the instrument, subject to operator inspection. Nerve fiber layer assessment. The procedure for evaluating the integrity of the NFL is similar to that described for evaluating the ON. The NFL is best visualized using digital photography or stereophotographic techniques with red-free illumination and highresolution black and white film. 207,208,268 Serial NFL examination is more sensitive than color ON evaluation in detecting the eyes conversion from OH to POAG. In one study, a minority of the eyes (about 20%) with OH that converted to glaucoma over a 5- year period showed changes in the ON, while about 50 percent showed developing or worsening atrophy of the NFL. 198 In another study, 60 percent of eyes with OH that converted to POAG had NFL defects at least 6 years before VF loss, and 88 percent had NFL defects at the time of the initial VF loss. 269 Technology for assessing the NFL in detecting and monitoring the progression of glaucoma has benefited from significant advances. Studies have investigated the capabilities of scanning laser polarimetry, OCT, and scanning laser ophthalmoscopy 278,279 in distinguishing normal and OH eyes from those with POAG, 271,272, as well as the reproducibility of results obtained with these instruments. 270,273 The study results are encouraging with respect to accurate measurement of NFL thickness, but whether these instruments have the sensitivity and specificity to detect the onset and the progression of glaucomatous damage remains to be determined. 277 The correlations between VF 30 Open Angle Glaucoma indices and peripapillary NFL thickness have been weak, ,279 and the distribution of parameters measured by these techniques in normal eyes overlaps measurements made in eyes with OH or both OH and POAG, thereby reducing the sensitivity and the specificity of these tests. 271,272 Peripapillary area assessment. Atrophy of the peripapillary area (PPA) occurs more frequently in eyes with glaucoma than in those with OH or in normal eyes IOP may not significantly affect the extent of PPA atrophy, 281,286,289,290 but atrophy in both zone alpha (peripheral to zone beta) and zone beta (bordering the optic nerve head) is significantly more extensive in eyes with glaucoma. 284,287 Zone beta atrophy occurs significantly more often in persons with glaucoma than in normal individuals, ,286,287 yet the measurement of zone beta may be of limited usefulness in the detection or follow-up of glaucoma. 280,282,291 There is a correlation between the loci of peripapillary atrophy and ON and VF damage ,287,292,293 In the normal eye, peripapillary atrophy is more extensive and more frequently located in the temporal horizontal sector. 282,284 The value of following the changes in PPA atrophy in glaucoma suspects or individuals with glaucoma has not been well established. 291,294 Some studies have found a correlation between the progression of PPA atrophy and the progression of both POAG 287,294,295 and NTG. 286,296 Others have found no significant difference between the prevalence of PPA atrophy in eyes with progressive glaucoma and those with nonprogressive OH. 200,280,291 In a study of 978 eyes in 511 Caucasian subjects, investigators followed 548 eyes with OAG (194, NTG), 289 with OH, and 141 without ON disease for 4.5 ± 2.4 years (median, 3.8 years; range: years). After average follow-up of nearly 4 years, they detected enlargement of the peripapillary zone beta in 16 eyes (1.6% of the 978), including 15 eyes (2.7%) with OAG and 1 (0.3%) with OH, but there was no zone beta enlargement in the normal eyes. After excluding eyes with a myopic refractive error

19 The Care Process 31 exceeding 3 D, they found zone beta enlargement significantly more often in eyes with progressive glaucoma (5/81 or 6.2%) than in eyes with nonprogressive glaucoma (3/354 or 0.8%; P < 0.001). Peripapillary atrophy (zone beta) increased in relatively few eyes with chronic OAG. In the refractive range above 3 D, zone beta enlargement occurred significantly more often (P < 0.001) in progressive glaucoma than in nonprogressive glaucoma. In view of its low frequency, enlargement of zone beta may not be very useful as a marker for glaucoma progression. 297 Fundus photography. As a means of improving accurate clinical diagnosis and follow-up, 298 stereoscopic fundus photography through a dilated pupil is preferable. Qualitative evaluation of the structural features of the ON, NFL, and surrounding PPA, and of function (VF parameters) by direct observation and the assessment of photographs may offer more diagnostic precision than quantitative evaluation (e.g., digital imaging analysis) in determining the presence of structural glaucomatous damage 203,299 at the stage of early VF loss. Evidence that optic disc hemorrhages were detected more frequently by evaluation of digital pictures of the retina than by assessment of the ON, 300 suggests that photographic documentation every 2 years is appropriate for establishing the baseline appearance of the ON, NFL, and the peripapillary layer, and that stereoscopic photography is indicated each time the ON or NFL changes in glaucoma suspects over time. 298 Visual fields. Measurement of threshold levels in areas of the VF likely to be affected by glaucomatous damage should be made by perimetry through a pupil of adequate size. 301 The results of perimetry should be compared with the reference values from an age-matched control population and evaluated with respect to the probability of abnormal (glaucomatous) findings. 302 The clinician should consider factors that can influence interpretation of the findings, including the patient's learning curve Open Angle Glaucoma c. Supplemental Testing Other procedures may be used to detect the earliest loss of visual function from glaucoma. Although measurement of color vision, contrast sensitivity, and dark adaptation, in addition to pattern electroretinograms and visual evoked potentials, have been thoroughly studied, none has proven ability to distinguish glaucoma suspects from individuals with POAG. 307 Tonography 308 and provocative testing 309 are of little value in the diagnosis of OAG, due to their poor sensitivity and specificity. 7 Short-wavelength automated perimetry (SWAP) may be useful in evaluating early or subtle diseases of the ON and retina. 310 A technique with which to isolate the blue color (short-wavelength) vision mechanism, SWAP appears to uncover loss of visual function earlier in the disease process than traditional white-on-white automated perimetry SWAP facilitates prediction of future defects that whiteon-white perimetry will eventually detect. 310,311,313,315 The VF defects found with SWAP are larger and progress more rapidly than those localized with white-on-white automated perimetry. 311,313 SWAP results, which may be predictive of which eyes with early glaucomatous VF loss are most likely to progress, 311 correlate with structural changes in the ON 316,317 and the NFL. 314 Moreover, an association between the prevalence of defects localized with SWAP and other risk factors is predictive of the development of glaucoma in patients with OH. 312,315 Of clinical concern, however, are the longer duration of testing and the fluctuation of patient responses that may occur with the use of SWAP. Threshold frequency doubling technology (FDT) perimetry may detect visual function loss when the standard white on white visual field is full. The changes can also be correlated with ON and NFL losses and are predictive of the development of glaucoma in patients with OH. 318

20 The Care Process Open Angle Glaucoma 2. Follow-up Glaucoma Evaluation Because the earliest detection of glaucoma may require clinical observation of very subtle changes in the appearance of the ON, NFL, PPA, or VF over several years, repeated evaluation, even within a 1-year period, may be needed for a definitive diagnosis. 200 Continual changes in any one of these parameters may facilitate the first clinical recognition of the earliest stages of glaucoma. 319 The person with one or more risk factors, who has a higher probability of developing POAG, needs more frequent evaluation to rule out the presence of the earliest clinical signs of glaucoma. This evaluation should be done at least yearly in the absence of complicating factors, but perhaps more often, depending on the person's relative risk of developing glaucoma. Follow-up evaluations are based on tests and procedures similar to those in the initial glaucoma evaluation. Less comprehensive follow-up examinations may be useful in assessing specific clinical parameters in glaucoma suspects. Follow-up evaluation of the patient with diagnosed OAG is similar to the procedure used to make the initial diagnosis of the disease. Patients need to be assessed in the first 1 2 years after diagnosis to ascertain whether the condition is stable or progressing. In approximately 10 percent of newly diagnosed patients, the OAG progresses rapidly, and such persons need to have their treatment regimen adjusted. Progression can only be discovered by performing optic disc evaluation, imaging, and perimetry at least yearly and in many cases more often. 180 Tests may include, but are not limited to the following assessments: 224,320 Blood pressure and pulse. Adrenergic agonists and betaadrenergic-blocking agents can adversely affect blood pressure and heart rate. Biomicroscopy. Examination of the lids, conjunctiva, cornea, and anterior and posterior chambers is needed to detect adverse reactions to therapy or signs of the development of secondary glaucoma. Tonometry. Diurnal IOP curves and IOP measurements with the patient in the supine position 321 may be needed for certain glaucoma patients, especially those with NTG. 322,323 Gonioscopy. To rule out the development of an angle closure component in the glaucoma, gonioscopy should be repeated periodically. This examination is more frequently needed in follow-up of patients on miotic therapy or in those who show changes in IOP. Optic nerve assessment. Stereoscopic examination of the ON, NFL, and PPA through a dilated pupil should be performed at least once per year, but may be needed more frequently in cases of advanced glaucoma. 299 Sequential stereoscopic photography or imaging technology can be valuable in detecting subtle changes in the ON or NFL. 203 Visible damage to the ON can occur early in the disease process, before detectable VF loss. 152,324 Once VF defects have been established, sequential perimetry may be a more sensitive indicator of progressive glaucomatous damage. 324 Patient history. In addition to a review of risk factors, the history should focus on changes in the patient's medical status or medications, side effects or adverse reactions to therapy, and compliance with prescribed therapy. 320 Visual acuity. Various forms of treatment for glaucoma as well as advanced stages of the disease can affect visual acuity. Nerve fiber layer assessment. Assessment of the NFL is similar to ON assessment but uses red-free illumination. The NFL can also be assessed with digital photography and imaging. In the early stages of glaucoma, estimation of structural abnormalities from serial NFL photographs may be more sensitive than assessment of the ON. 200